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Management – New Options

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1 Management – New Options
Seizures Management – New Options

2 Formulary Zonisamide (Zonegran) 5-10mg/kg BID 25,50,100mg capsules
Levetiracetam (Keppra) 20-60mg/kg TID 250mg, 500mg, 750mg Pregabalin (Lyrica) 2-4mg/kg BID 25, 50, 75, 100, 150, 200, 225, and 300 mg capsules Rufinamide (Banzel) 10-20mg/kg BID 200mg, 400mg tablets Topiramate (Topomax) 2-5mg/kg BID 25, 50mg tablets Gabapentin (Neurontin) 10-30mg/kg T-QID 100, 300, 400, 600, 800mg Capsules/tablets

3 Formulary Lacosamide (Vimpat) 100-200mg BID (humans)
50, 100, 150, 200mg tablets Clobazam (Onfi) 0.5mg/kg BID? 5, 10, 20mg tablets Stiripentol (Diacomit) mg/kg/day B-TID 250, 500mg tablets, suspension BI Anticonvulsant…..

4 Don’t USE Formulary KBr – Respiratory toxic in Cats
Lamotrigine (Lamictal) – cardiotoxic in dogs Verapamil – no effect Dilantin Depakote/Depakene Primidone

5 New Seizure Pearls NCSU - ABCB1 Gene Defect – Easier to control epileptics Denmark - Belgian Shepherd Epilepsy Study – normal life span but epilepsy percentage of reasons for death (also 2 SUEDS). England – 41% of epileptics had clusters – no age, breed predilection but intact animals had more clusters Korea – Zonisamide 60% effective sole agent

6 Auburn – Seizure control - 85% pheno 52% KBr
Minnesota – Status – 60mg/kg Keppra – once significant improvement in control England – Juvenile onset <1y seizures – 22% remission rate (humans 60%). NCSU - The pharmacokinetics of levetiracetam in healthy dogs concurrently receiving phenobarbital. PB lowered LEV levels

7 Germany - CSF Glucose – not indicative of infection – just inflammation
TAMU – PSS surgery – pre treat with Keppra no seizures vs 4/84 Denmark – PBGV – 9% epileptics England – Seizures and brain tumors - 68 dogs (42 had seizures 24 did not). Contrast enhancement, frontal lobe and herniation - risks

8 LV Nevada - Canine and feline epileptic seizures and the lunar cycle: 2,507 seizures ( ) dogs – no correlation Penn - A novel implanted device to wirelessly record and analyze continuous intracranial canine EEG. Treat only when going to have seizure! England - Effects of essential fatty acid supplementation in dogs with idiopathic epilepsy: a clinical trial. No effect – blinded placebo controlled.

9 Germany - Add-on treatment with verapamil in pharmacoresistant canine epilepsy. – Bradycardia and hypotension – no effect

10 Non Epileptic Attacks Breath holding Episodes Reflex syncope benign paroxysmal vertigo vasovagal attacks sleep disorders pseudoseizures munchhausen syndrome EEG – 20% have normal EEG Truly normal or “out of reach of electrodes” improve by sleep deprivation; flashing lights; hyperventilation; prolonged periods

11 Spot 12 year old Chihuahua Cluster/isolated seizures
Meds: Phenobarbital, Kbr, gabapentin, clorazepate Zonisamide

12 Rex 9y Lab Mix Pheno, Kbr, Lyrica, gabapentin, Zonisamide, valproic acid, acetazolamide, banzel

13 Generalized seizures. Absence seizures, appear to be staring into space These seizures are sometimes referred to as petit mal seizures, which is an older term. Tonic seizures cause stiffening of muscles of the body Clonic seizures cause repeated jerking movements of muscles on both sides of the body. Myoclonic seizures cause jerks or twitches of the upper body, arms, or legs. Atonic seizures cause a loss of normal muscle tone - will fall down or may drop head involuntarily. Tonic-clonic seizures cause a mixture of symptoms, older term: grand mal seizures. 13

14 Simple focal motor seizure
Remain conscious - sudden focal jerking of a muscle group Complex focal seizure Change in or loss of consciousness. dreamlike experience. may display strange, repetitious behaviors (automatisms) such as blinks, twitches, mouth movements, walking in a circle. 14

15 Human Experience 60% of childhood epilepsy resolves and 60% controlled with monotherapy 60 percent of people with epilepsy have focal seizures. These seizures are frequently described by the area of the brain in which they originate. 15

16 Anticonvulsant History
Bromide first used in the late 1800’s Negative side effects made it a less than ideal medication Discontinued in 1912 in US Reappeared in 1980’s for veterinary use Used in Europe for people Phenobarbital 1912 Despite its shortcomings, phenobarbital became the main drug prescribed for epilepsy for the next 26 years.

17 Anticonvulsant History
Phenytoin (Dilantin) was introduced in 1938 is still a major drug used today in human seizure control. From 1945 to 1960 a series of anticonvulsant drugs based on trimethadione (Tridione) Diazepam 1963 Carbamazepine (Tegretol) 1974 Valproic acid (Depakene) 1978

18 Drugs not routinely used in veterinary medicine
Primidone Carbamazepine (Tegretol, Carbatrol) Phenytoin (Dilantin) Valproic acid (Depakene)/Divalproex (Depakote) Ethosuximide (Zarontin)/Methsuximide (Celontin)

19 Anticonvulsant Recent History
In the 1990’s another crop of new medications appeared These drugs are reported to have fewer side effects, but with similar efficacy (questionable) in the control of seizures

20 When/Why to Start Treatment
More than 1 seizure in a 4-6 week period Active intracranial disease (neoplasia, inflammation) Cluster seizures Status epilepticus

21 Clinical findings, treatment, and outcome of dogs with status epilepticus or cluster seizures: 156 cases ( ). J Am Vet Med Assoc. 1999 Nov 15;215(10): Bateman SW, Parent JM. Underlying causes of seizures were primary epilepsy (26.8%), secondary epilepsy (35.1%;), reactive epileptic seizures (6.7%), primary or secondary epilepsy with low serum antiepileptic drug concentrations (5.7%), and undetermined (25.8%). 186 resulted in admission to the ICU. CRI of diazepam or phenobarbital Of 194 admissions, 74.7% (145) resulted in discharge from the hospital 2.1% (4) in death, and 23.2% (45) in euthanasia. Poor outcome (death or euthanasia) was significantly associated with GME, loss of seizure control after 6 hours of hospitalization, and the development of partial status epilepticus. 21 21

22 MOA – Mechanisms Of Action

23 MOA Carboxylic acids/ Fatty acid derivatives
GABA transaminase inhibitor - Valproic acid GABA reuptake inhibitor - Tiagabine GABA analogs 1. Gabapentin, Pregabalin, Vigabatrin Channel Blockers Sodium Fosphenytoin, Phenytoin Carboxamides Carbamazepine,Oxcarbazepine, Rufinamide Calcium Ethosuximide Channel Openers 1. Potassium - retigabine 23

24 Unknown/ungrouped Phenyltriazines - Lamotrigine
Oxazolidinediones Ethadione, Paramethadione, Trimethadione Ureas – Phenacemide, Pheneturide Monosaccharides - Topiramate

25 25

26 Felbamate (Felbatol) Dicarbamate medication approved for use in 1993
Increases seizure threshold and prevents seizure spread by reducing excitatory neurotransmission in the brain In dogs used as an add on for refractory seizures, not generally used as monotherapy Generic 9/2011.

27 Felbamate (Felbatol) Undergoes hepatic metabolism by P450 system and is also excreted by the kidneys T1/2 5-6 hours with steady state reached in 1-2 days Dose mg/kg q8 hours, has been used as high as 65 mg/kg Non sedating with a high margin of safety Idiosyncratic aplastic anemia secondary to bone marrow suppression and liver toxicity Similar but rare and reversible hepatotoxicity and blood dyscrasias seen in dogs Monitoring Parameters CBC, chemistry at 1 month after starting treatment, then q 3-6 months

28 Treatment of partial seizures and seizure-like activity with felbamate in six dogs.
J Small Anim Pract. 2001 Aug;42(8):403-8.Ruehlmann D, Podell M, March P. Six dogs with partial seizures or partial seizure-like activity Median duration of therapy was nine months (range two to 22 months). All dogs experienced a reduction in seizure frequency after felbamate administration. Reversible haematological adverse effects were detected in two dogs, with one dog developing concurrent keratoconjunctivitis sicca. 28 28

29 Gabapentin (Neurontin)
Designed to mimic GABA, but does not have similar pharmacological properties of GABA nor does it bind to GABA receptors Facilitates transport of GABA out of cells to act on the GABAA receptor to increase inhibitory activity and block sodium channels Undergoes partial hepatic metabolism, but mostly excreted by the kidneys

30 Treatment with gabapentin of 11 dogs with refractory idiopathic epilepsy.
Vet Rec Dec 23-30;159(26): TPlatt SR, Adams V, Garosi LS, Abramson CJ, Penderis J, De Stefani A, Matiasek L. 11dogs with refractory idiopathic epilepsy All had generalised tonic-clonic seizures and had been treated with a combination of phenobarbital and potassium bromide Compared for the three months before and after Six of the dogs showed a positive response. minimum 50 per cent reduction in the number of seizures per week was interpreted as a positive response Mild side effects of ataxia and sedation were observed in five of the dogs, but they were not severe enough to warrant the treatment being discontinued during the trial. 30

31 Improving seizure control in dogs with refractory epilepsy using gabapentin as an adjunctive agent
Aust Vet J Oct;83(10): Govendir M, Perkins M, Malik R. Faculty of Veterinary Science, Building B14, The University of Sydney, New South Wales DESIGN: 17 dogs;16 of which have idiopathic epilepsy. PROCEDURE: Patients were stabilised using phenobarbitone and/or potassium bromide and dosed additionally with gabapentin at 35 to 50 mg/kg/d (divided twice or three times daily) for 4 months. RESULTS: There was no significant decrease in the number of seizures over the study period for the entire cohort, however three dogs stopped seizuring completely. Side effects observed - sedation and hind limb ataxia. Long-term, a further two patients became seizure free and ten patients remained on gabapentin indefinitely. No long-term side effects have become apparent. CONCLUSION: Addition of gabapentin increased the interictal period and shortened the post-seizure recovery in some canine epileptics. In some dogs, seizures were prevented completely, while in others there was an increase in interictal period. Owners recorded seizure activity and side effects during this period in a standardised diary. Patients underwent monthly physical examinations and venepuncture to assess selected serum biochemical analytes, as well as phenobarbitone and bromide concentrations. Patients were further monitored for long-term response to adjunctive gabapentin therapy. There was a significant increase in the number of patients who showed an increase in the interictal period (P > 0.001). 31

32 Zonisamide (Zonegran)
                                                           Sulfonamide based drug that became available for use in 2000 Is used in human for treatment of focal and generalized seizures with minimal side effects Works by blocking the propagation of epileptic discharges and suppressing focal epileptogenic activity

33 Zonisamide (Zonegran)
Metabolized mainly by hepatic microsomal enzymes, but does not induce P450 system T1/2 15 hours Dose 10 mg/kg q 12 hours, but if add on treatment with drugs inducing hepatic enzymes, decrease dose to 5 mg/kg q 12 hours High margin of safety Can be used as monotherapy Side effects Transient sedation, ataxia, inappetance, metabolic acidosis, liver intoxication, bone marrow Can reduce side effects by gradually increasing the dose If being used with phenobarbital, recommend reducing phenobarbital dose by 25% T1/2 15 hours, but is shown to be shorter in patients already on drugs that stimulate hepatic enzymes (i.e. phenobarbital – increase dose or frequency)

34 Zonisamide therapy for refractory idiopathic epilepsy in dogs.
J Am Anim Hosp Assoc Jul-Aug;40(4):285-91 Dewey CW, Guiliano R, Boothe DM, Berg JM, Kortz GD, Joseph RJ, Budsberg SC. Department of Surgery, Long Island Veterinary Specialists, Plainview, New York Twelve dogs with poorly controlled idiopathic epilepsy were entered into a prospective, open-label, noncomparative study. Oral zonisamide was administered as an additional therapy at a dosage adequate to achieve serum drug concentrations of 10 to 40 microg/mL. Seizure frequency before and after initiation of zonisamide therapy was recorded. A dosing interval of q 12 hours was sufficient to maintain serum zonisamide concentrations within the therapeutic range. The mean dosage of zonisamide required was 8.9 mg/kg q 12 hours. Seven (58%) dogs responded favorably, experiencing a mean reduction in seizures of 81.3%. Five dogs had an increase in seizure frequency. Mild side effects (e.g., transient sedation, ataxia, vomiting) occurred in six dogs. 34

35 Prospective study of zonisamide therapy for refractory idiopathic epilepsy in dogs
J Small Anim Pract Mar;48(3): von Klopmann T, Rambeck B, Tipold A. Department of Small Animal Medicine and Surgery, University of Veterinary Medicine Bischofsholer Damm Hannover, Germany. METHODS: Thirteen dogs fulfilled the inclusion criteria of poor seizure control despite adequate serum levels of phenobarbital, potassium bromide or both. One further dog was treated with zonisamide as monotherapy because of severe blood dyscrasia due to phenobarbital treatment.. RESULTS: Data of 11 dogs could be evaluated: nine of them were responders. The median reduction of seizure frequency of all dogs on zonisamide add-on therapy was 70 per cent (range 14 to 100 per cent). Only transient central nervous system side effects were reported. No further increase of liver enzymes occurred. In three of the responder dogs, seizure control subsided after individual time periods (between 69 days and seven months). Various seizure parameters were evaluated retrospectively for a four month period without zonisamide and prospectively for the same time period under zonisamide add-on therapy. The study time period was extended by up to 17 months to evaluate long-term outcome 35

36 Topiramate (Topamax) Sulfamate substituted monosaccharide
Blocks seizure spread by rapidly potentiated GABA activity in the brain In people it is used for generalized and partial seizures                                In people it is primarily excreted by the kidneys unchanged T1/ hours (people), 2-4 hours (dogs), steady state reached in 1-3 days Dose 2-10 mg/kg q 12 hours, best to start low Side effects GI upset, inappetence, irritability, ataxia

37 Levetiracetam (Keppra)
Synaptic Vesicle Protein 2 A, is required for normal nervous system functioning and is the binding site of the anti- epilepsy drug levetiracetam Mostly excreted unchanged in the urine, the remainder is hydrolyzed in the serum and by other organs No hepatic metabolism in humans or dogs T1/2 3-4 hours but may exert anticonvulsant effects that last longer than its presence in the bloodstream Dose 20 mg/kg q 8 hours

38 The efficacy and tolerability of levetiracetam in pharmacoresistant epileptic dogs.
Vet J. 2008 Jun;176(3): Epub 2007 Apr 30. Volk HA, Matiasek LA, Luján Feliu-Pascual A, Platt SR, Chandler KE. 8/14 dogs responded significantly to the treatment and seizure frequency was reduced by 50%. In dogs that remained refractory, the dosage was increased to 20 mg/kg TID for 2 months. One further dog responded to levetiracetam treatment. Levetiracetam responders had a significant decrease in seizure frequency of 77% (7.9+/-5.2 to 1.8+/-1.7 seizures/month) and a decrease in seizure days per month of 68% (3.8+/-1.7 to 1.2+/-1.1 seizure days/month). However, 6/9 responders experienced an increase in seizure frequency and seizure days after 4-8 months continuing with the levetiracetam treatment at the last effective dosage. 38 38

39 Levetiracetam as an adjunct to phenobarbital treatment in cats with suspected idiopathic epilepsy.
J Am Vet Med Assoc. 2008 Mar 15;232(6): Bailey KS, Dewey CW, Boothe DM, Barone G, Kortz GD. ANIMALS: 12 cats suspected to have idiopathic epilepsy that was poorly controlled with phenobarbital or that had unacceptable adverse effects PROCEDURES: Cats were treated with levetiracetam (20 mg/kg [9.1 mg/lb], PO, q 8 h). RESULTS:  Median seizure frequency prior to treatment with levetiracetam (2.1 seizures/mo) was significantly higher than median seizure frequency after initiation of levetiracetam treatment (0.42 seizures/mo0 7 of 10 cats were classified as having responded Two cats had transient lethargy and inappetence. After a minimum of 1 week of treatment, serum levetiracetam concentrations were measured before and 2, 4, and 6 hours after drug administration, and maximum and minimum serum concentrations and elimination half-life were calculated. Seizure frequencies before and after initiation of levetiracetam treatment were compared, and adverse effects were recorded. Median maximum serum levetiracetam concentration was 25.5 microg/mL, median minimum serum levetiracetam concentration was 8.3 microg/mL, and median elimination half-life was 2.9 hours. 39 39

40 Pregabalin (Lyrica) Structural analogue to GABA
No effect on GABA receptors Renal excretion T1/2 6 ½ hours (people) Current study in dogs dose 2-4 mg/kg q 12 hours

41 Pregabalin as an adjunct to phenobarbital, potassium bromide, or a combination of phenobarbital and potassium bromide for treatment of dogs with suspected idiopathic epilepsy. J Am Vet Med Assoc Dec 15;235(12): Dewey CW, Cerda-Gonzalez S, Levine JM, Badgley BL, Ducoté JM, Silver GM, Cooper JJ, Packer RA, Lavely JA. Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY OBJECTIVE: Pregabalin as an adjunct to phenobarbital, potassium bromide ANIMALS: 11 client-owned dogs RESULTS: Seizures were significantly reduced (mean, 57%; median, 50%) after pregabalin administration 9 dogs that completed the study; 7 were considered responders with mean and median seizure reductions of 64% and 58%, respectively. Adverse effects for pregabalin were reported in 10 dogs. PROCEDURES: Dogs were treated with pregabalin (3 to 4 mg/kg [1.4 to 1.8 mg/lb], PO, q 8 h) for 3 months. Number of generalized seizures in the 3 months before and after initiation of pregabalin treatment was recorded. Number of responders (>or= 50% reduction in seizure frequency) was recorded, and seizure frequency before and after initiation of pregabalin treatment was compared by use of a nonparametric Wilcoxon signed rank test. 41

42 Rufinamide (Banzel) No published clinical studies in dogs
One published pharmacokinetic study Dose 10-20mg/kg BID Clinical experience – good 42

43 Rufinamide: a new antiepileptic medication for the treatment of seizures associated with lennox-gastaut syndrome. Ann Pharmacother. 2010 Apr;44(4): Epub 2010 Mar 16. Wisniewski CS. STUDY SELECTION AND DATA EXTRACTION: Published controlled trials DATA SYNTHESIS: Rufinamide is a new antiepileptic agent that differs structurally from other antiepileptic drugs and is approved as adjunctive therapy for Lennox- Gastaut syndrome (LGS). I prolonging sodium channel inactivity, stabilizing cell membranes It is absorbed and metabolized extensively, then excreted renally as an inactive metabolite. Clinical trials show that adjunctive rufinamide is effective at reducing seizure frequency in patients with LGS and refractory partial seizures rufinamide is well tolerated, causing headache, dizziness, and fatigue at rates of >10%. CONCLUSIONS: Data show that rufinamide is safe and effective as an adjunctive agent for LGS and may be used to treat partial seizures. OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of rufinamide in the treatment of epileptic seizures and describe its potential place in therapy. DATA SOURCES: MEDLINE (1966-January 2010) and PubMed (1966-January 2010) literature searches were conducted to identify primary literature investigating rufinamide. References from selected publications discussing rufinamide, as well as the package insert, were reviewed. 43 43

44 Lacosamide (Vimpat) No clinical studies in dogs Renal excretion 44

45 Clobazam Benzodiazepine (5,10,20mg) $3-4/pill 2.5mg/kg TID? 45

46 Stiripentol Initial dose is 50 mg/kg per day. This may be increased up to 100 mg/kg per day, with a maximum of 4g B-TID 250 mg, 500 mg capsules; suspension Inhibits cytochrome P450 46

47 The third-generation AEDs consist of 20 novel drugs
brivaracetam (BRI), carabersat (CRB), carisbamate (CBM), DP-valproic acid (DP-VPA), eslicarbazepine acetate (ESL), fluorofelbamate (FFBM), fosphenytoin (FPHT), ganaxolon (GNX), lacosamide (LCM), losigamone (LSG), pregabaline (PGB), remacemide hydrochloride (RMC), retigabine (RTG), rufinamide (RUF), safinamide (SAF), seletracetam (SEL), soretolide (SRT), stiripentol (STP), talampanel (TLP) and valrocemide (VLR). 47


49 Epilepsy Surgery 3 drug failures
Impaired consciousness, injury, stigmatizing behavior (disrobing, uttering obscenities), noxious auras (vomiting/fear) At least 1/month CPS and Tonic/Clonic – most common 50% of intractable patients have surgically remediable epilepsy Control after sx 58% seizure free vs 8% with continued drug management in one study Workup – EEG, MRI, neuropsychological evaluation. If not definitive then invasive EEG, nuclear med (PET, SPECT) and WADA (sodium amylobarbital) test. 49 49

50 Syndromes Amenable to Surgery:
Mesial Temporal Lobe Epilepsy (hippocampus and amygdala); Frontal Lobe epilepsy; Lesional Partial Epilepsy; Crytogenic Neocortical Epilepsy Surgery options Lesionectomy, lobectomy, hemispherectomy, subpial transections, corpus collosotomy Success rates; Anterior temporal lobectomy 70% success; other areas 40-60% seizure free; CC 50-80% reduction Deficits – some are expected. Many transient. 50% minor field of vision loss. 1-2% permanent morbidity. 50

51 Electrostimulation procedures
Vagal Nerve Stimulations Deep Brain Stimulations

52 VNS Does not eliminate seizures 27-64% reduction 52

53 53

54 Use of vagal nerve stimulation as a treatment for refractory epilepsy in dogs.
JAVMA 2002 Oct 1;221(7): Munana KR, Vitek SM, Tarver WB, Saito M, Skeen TM, Sharp NJ, Olby NJ, Haglund MM ANIMALS: 10 dogs with poorly controlled seizures. RESULTS: No significant difference overall 13-week treatment. During the final 4 weeks of the treatment period, a significant decrease in mean seizure frequency (34.4%) was detected. Complications included transient bradycardia, asystole, and apnea during intraoperative device testing, and seroma formation, subcutaneous migration of the generator, and transient Horner's syndrome. PROCEDURE: A programmable pacemaker-like device designed to deliver intermittent stimulation to the left cervical trunk of the vagus was surgically implanted in each dog. Dogs were assigned randomly to two 13-week test periods, 1 with nerve stimulation and 1 without nerve stimulation. Owners recorded data on seizure frequency, duration, and intensity, as well as adverse effects.

55 Personal Experience 1 DDB (Gaia) 1 Husky (Stoli)
Reason: Spinal deformity and epilepsy Outcome: Initially good (lowered meds); lead complication 1 Husky (Stoli) Severe clusters – numerous medications Short lived improvement then DOA

56 56


58 Hemispherectomy

59 59

60 Rassmusen's Encephalitis
Indications Rassmusen's Encephalitis Hemimegaloencephaly Sturge Weber Syndrome



63 Risks of Hemispherectomy
Hemorrhage is a risk for hemispherectomy. Disseminated intravascular coagulation "Aseptic meningitis," Hydrocephalus, 20–30% of patients. Death from surgery - approximately 2% of patients. 63 63

64 Behav Brain Res. 1986 May;20(2):217-30.
Recovery of functions after neonatal or adult hemispherectomy in cats. III. Complex functions: open field exploration, social interactions, maze and holeboard performances. Behav Brain Res May;20(2): Burgess JW, Villablanca JR, Levine MS. Complex behavioral patterns were studied in cats with removal of the entire left cerebral hemisphere neonates (n = 10) or adults (n = 11); control (n=24) Adult cats showed decreased open field activity in locomotion, rearing and sniffing. Kittens showed similar deficits at 100 days of age by 150 days of age they resembled normal littermates in all 3 measures. 64

65 Recovery of function after neonatal or adult hemispherectomy in cats:
Behav Brain Res Mar;19(3): Villablanca JR, Burgess JW, Olmstead CE. Cats with removal of the left hemitelencephalon (hemispherectomy) as neonates (n = 12) or in adulthood (n = 14), were compared using a battery of 16 neurological and behavioral tests given when they were young adults (kittens) or at least 5 months after the lesion (adults). The neonatal-lesioned subjects grew normally and performed markedly and significantly better than adult- lesioned cats None of the animals recovered tactile placing of the right forelimb or a normal vision in the right visual field. Overall recovery was outstanding for all cats Neonatal-lesioned were hard to differentiate from intact controls in their spontaneous, daily activities. in 13 tests covering the wide range of movement, posture and sensory functions which were assessed. 65

66 Proc Staff Meet Mayo Clin. 1959 Jan 7;34(1):13-22.
Operative technics and principles utilized in total hemispherectomy in the monkey and the dog. WHITE RJ, MACCARTY CS, GRINDLAY JH, SCHREINER LH. 66

67 Absence of temporal lobe epilepsy pathology in dogs with medically intractable epilepsy.
J Vet Intern Med Jan-Feb;16(1):95-9. Buckmaster PS, Smith MO, Buckmaster CL, LeCouteur RA, Dudek FE. Department of Comparative Medicine, Stanford University School of Medicine, CA Temporal lobe epilepsy is the most common type of epilepsy in adult humans, it is frequently resistant to anticonvulsant therapy We sought to test the hypothesis that dogs with medically intractable epilepsy have temporal lobe epilepsy. The hippocampi of 6 dogs that were euthanized because of chronic, recurrent seizures were compared with those of 8 nonepileptic controls. These findings demonstrate a lack of hilar neuron loss and granule cell axon reorganization, suggesting that temporal lobe epilepsy is not a common cause of medically intractable epilepsy in dogs. In control and epileptic dogs, stereological cell counting showed similar numbers of neurons in the hilus of the dentate gyrus, somatostatin immunoreactivity identified numerous immunopositive neurons in the hilus, and Timm staining showed the normal pattern of granule cell axon projections. 67 67

68 Callosotomy J Neurosurg Sci Mar;41(1):51-7. Callosotomy for intractable epilepsy: overall outcome. Rougier A, Claverie B, Pedespan JM, Marchal C, Loiseau P. Clinique Universitaire de Neurochirurgie, Hôpital Pellegrin-Tripode, Bordeaux, France. Atonic and tonic astatic seizures characterized both by clinical and electroencephalographical specific patterns, are the most responsive. > 50% reduction in seizure frequency to a complete cessation, in 60 to 80% of the patients. For tonic-clonic seizures, favorable outcome fluctuates from 40% to 80% principally according to the extension of the section. Other types of seizures are not indicated for callosotomy even though some improvement may be observed. Actual benefits are in close connection with both seizure relief and age at operation. To obtain a gain in social independence not only seizure control has to be better but also surgery must be performed sooner. 68

69 69

70 70

71 Multiple Subpial Transections

72 Young Dog - Healthy Phenobarbital Potassium bromide Zonisamide

Levetiracetam (Keppra) or zonisamide (Zonegran) Felbamate (Felbatol)

74 Liver Disease Levetiracetam (Keppra) or Potassium Bromide
Gabapentin (Neurontin) Pregabalin (Lyrica) Topiramate (Topimax)

75 Refractory Combos Phenobarbital and levetiracetam
Phenobarbital and KBr (side effects) Zonisamide and KBr Zonisamide and levetiracetam Phenobarbital and zonisamide (double zonisamide)

76 Severely Refractory Refer?
Rufinamide/Banzel Lacosamide Clobazam Surgery


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